Targeted-Capture Next-Generation Sequencing in Diagnosis Approach of Pediatric Cholestasis

被引:7
|
作者
Almes, Marion [1 ,2 ,3 ]
Spraul, Anne [2 ,3 ,4 ]
Ruiz, Mathias [5 ]
Girard, Muriel [6 ]
Roquelaure, Bertrand [7 ]
Laborde, Nolwenn [8 ]
Gottrand, Frederic [9 ]
Turquet, Anne [10 ]
Lamireau, Thierry [11 ]
Dabadie, Alain [12 ]
Bonneton, Marjorie [13 ]
Thebaut, Alice [1 ,2 ]
Rohmer, Babara [5 ]
Lacaille, Florence [6 ]
Broue, Pierre [8 ]
Fabre, Alexandre [7 ]
Mention-Mulliez, Karine [9 ]
Bouligand, Jerome [3 ,14 ,15 ]
Jacquemin, Emmanuel [1 ,2 ,3 ]
Gonzales, Emmanuel [1 ,2 ,3 ]
机构
[1] Paris Saclay Univ, Bicetre Hosp,Reference Ctr Biliary Atresia & Gene, Assistance Publ Hop Paris AP HP,ERN RARE LIVER, Pediat Hepatol & Pediat Liver Transplant Unit,FSM, F-94270 Le Kremlin Bicetre, France
[2] Paris Saclay Univ, Hepatinov, INSERM UMR S 1193, F-91400 Orsay, France
[3] AP HP, Plateforme Expertise Malad Rares Paris Saclay, F-94270 Le Kremlin Bicetre, France
[4] Paris Saclay Univ, Bicetre Hosp, AP HP, Biochem Unit,DMU15, F-94270 Le Kremlin Bicetre, France
[5] Bron Hosp, Hepatol & Nutr Unit, Pediat Gastroenterol, F-69677 Lyon, France
[6] Hop Necker Enfants Malad, Hepatol & Nutr Unit, Pediat Gastroenterol, F-75015 Paris, France
[7] Marseille Univ Hosp, Pediat Gastroenterol Hepatol & Nutr Unit, F-13288 Marseille, France
[8] Toulouse Hosp, Pediat Gastroenterol Hepatol & Nutr Unit, F-31300 Toulouse, France
[9] Univ Lille, Dept Pediat Gastroenterol Hepatol & Nutr, INSERM U1286, CHU Lille, F-59000 Lille, France
[10] St Denis Hosp, Pediat Gastroenterol Hepatol & Nutr Unit, F-97405 La Reunion, France
[11] Bordeaux Hosp, Pediat Gastroenterol Hepatol & Nutr Unit, F-33076 Bordeaux, France
[12] Rennes Hosp, Pediat Gastroenterol Hepatol & Nutr Unit, F-35033 Rennes, France
[13] Nancy Hosp, Pediat Gastroenterol Hepatol & Nutr Unit, F-54035 Nancy, France
[14] Paris Saclay Univ, Bicetre Hosp, AP HP, Mol Genet Pharmacol & Hormonol Unit, F-94270 Le Kremlin Bicetre, France
[15] Paris Saclay Univ, Endocrine Physiol & Physiopathol, INSERM UMR 1185, F-94270 Le Kremlin Bicetre, France
关键词
genetic cholestasis; children; NGS; neonatal sclerosing cholangitis; PFIC; Alagille syndrome; transient neonatal cholestasis; NEONATAL CHOLESTASIS; MOLECULAR DIAGNOSIS; GENE-MUTATIONS; DEFICIENCY; VARIANTS; CHILDREN; ASSOCIATION; HEPATOLOGY; DISORDERS; CONSENSUS;
D O I
10.3390/diagnostics12051169
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Cholestasis is a frequent and severe condition during childhood. Genetic cholestatic diseases represent up to 25% of pediatric cholestasis. Molecular analysis by targeted-capture next generation sequencing (NGS) has recently emerged as an efficient diagnostic tool. The objective of this study is to evaluate the use of NGS in children with cholestasis. Methods: Children presenting cholestasis were included between 2015 and 2020. Molecular sequencing was performed by targeted capture of a panel of 34 genes involved in cholestasis and jaundice. Patients were classified into three categories: certain diagnosis; suggested diagnosis (when genotype was consistent with phenotype for conditions without any available OMIM or ORPHANET-number); uncertain diagnosis (when clinical and para-clinical findings were not consistent enough with molecular findings). Results: A certain diagnosis was established in 169 patients among the 602 included (28.1%). Molecular studies led to a suggested diagnosis in 40 patients (6.6%) and to an uncertain diagnosis in 21 patients (3.5%). In 372 children (61.7%), no molecular defect was identified. Conclusions: NGS is a useful diagnostic tool in pediatric cholestasis, providing a certain diagnosis in 28.1% of the patients included in this study. In the remaining patients, especially those with variants of uncertain significance, the imputability of the variants requires further investigations.
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页数:17
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